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Flashcards in Virus Genetics Deck (20)
1

Types of virus genomes

-DNA or RNA but not both
-single or double stranded
-single stranded RNA can be segmented or nonsegmented
-linear or circular

2

Size of viruses

-Parvoviruses- 2 genes
-Retroviruses- 3 genes
-Papillonaviruses- about 8 genes
-Adenoviruses- about 10 genes
-Herpes viruses- 70 genes and more
-Pox viruses- 200 genes

viruses have too few genes to survive independently, and depend on cellular genes to supply the missing functions

3

Gene expression in viruses

-regulated by cellular transcription factors
-Papillomavirus gene expression is regulated by keratinocyte factors, thus making the virus skin specific

4

Viruses are efficient

-no space is wasted
-100 percent of genome encoding protein or tRNA
-reading frames can overlap
-ribosomal frame shifting- known as translational frameshifts, due to ribosome slipping 1 or 2 bases on RNA
-alternative splicing of RNA
-cleavage of polyproteins by viral proteases (drug target)

5

Genome structures

-simple genomes- Retrovirus- genes linear on one RNA strand, with one promoter

-complex genomes- adenoviruses, herpesviruses, poxviruses- genes on both strands of DNA, often over lapping and each with its own promoter

6

Virus high mutation frequency

-high error rate of polymerase
-lack of proofreading and error correction
-lack of second strand in some viruses

-all types of mutations: point mutations, deletions, insertions, recombinations and rearrangements, insertion to host cell genome

7

Virus mutations

-allow epidermiological studies
-can allow live vaccines to be made
-can produce new antigens which avoid immunity
-can lead to drug resistance
-integration of viral genome can cause disease

8

Complementation

when a gene function of one virus replaces a mutated gene of another. Allows defective viruses to replicate and express their genes. Allows cell lines to support vaccine productio

9

Phenotype mixing of similar viruses

-exchange of capsid proteins
-if two polio virus serotypes infect the same cell the progeny might have capsids that are a mix of each serotype

10

Pseudotype virus

-the genetic material of one virus in the capsid or envelop of another

11

Recombination of homologous viruses

-the exchange of genes by crossing over at regions of homology. Produces a hybrid virus which reproduces- Western equine encephalitis virus

12

Reassortment of segmented viral genomes

-the rearrangement of parts of a segmented genome to form a new set of segments
-eg infuenza virus- antigenic shift
-reovirus (adenovirus)

13

Virus interference

-infection by one virus tends to prevent infection by another by:
-blocking of receptors
-competition for resources
-production of interferon or other anti-viral agents

14

Viral insertion mutations

-when a virus inserts like HIV it can interrupt the normal host genome and affect transcription in this way too

15

Development of Gene Therapy Viruses

-deletion of essential gene- insert that gene into packaging cell
-clone the therapeutic gene to virus
-grow the virus in the packaging cell
-test in cells- animals- humans

16

Diseases that might be treated by gene therapy

-hemophilia
-immune deficiencies
-retinal disorders
-liver enzymes deficiencies
-cystic fibrosis
-cancer: tumor suppressor genes, silencing of oncogenes, immune response genes, toxic or suicide genes, replicating cytotoxic viruses

17

Delivery of gene therapy by certain viruses

-delivery of gene therapy by viruses requires mutants whose replication is severely restricted
-they can be made from:
Retroviruses (mouse viruses, or HIV)
Adenoviruses
Herpes Simplex Virus
Adeno-associated virus

18

Problems with gene therapy

-short/ transient expression of foreign gene
-low efficiency of gene transfer
-inflammation in response to the virus- requirement for very high doses of virus vectors
-potential for chromosomal disturbances by virus

19

Gene therapy virus side effects

-Jesse Gelsinger- ornithine transcarbamylase deficiency, clinical trial with OTC in adenovirus into hepatic artery, developed acute respiratory distress syndrome
-Jolee Mohr, adalimumab, AAV/TNF blocker into knee died of systemic histoplasmosis
-SCID-X1, mouse leukemia virus modified to transduce stem cells, some developed T cell leukemia

20

Future research on gene therapy

-mutated viruses that cause less imflammation
-viruses that target a specific tissue
-conditionally replicating viruses
-non-viral methods of transfer of genes